The Bioanalytical Core Laboratory will provide state of the art and innovative bioanalytical expertise and techniques for the quantification of drugs and their metabolites, endogenous chemicals and other molecules of biological significance in new collaborative studies with the other cores in the center and all the funded drug abuse biomedical researchers at this and neighboring universities. These analyses will provide the expertise to perform new and innovative research and to enhance currently funded research projects in ways not anticipated at the time of their application submission. This core will accomplish these goals by making available reliable, validated mass spectrometric analysis of biological and non-biological materials for new projects as well as for NIDA sponsored and other researchers studying the mechanism of action of abused substances and addiction. The laboratory will develope methods will focus on the identification and quantification in biologic specimens of drugs and/or drug metabolites, such as cocaine, nicotine, cotinine, tetrahydrocannabinol (THC), JWH-018, JWH-073, CP 47,497, methadrone and methylene, as well as physiologically active small endogenous molecules and/or their metabolites such as anandamide, other endocannabinoids, prostamides and ceramide metabolites of sphingomelingolipids. These analyses will enhance the pharmacological studies of drugs of abuse by providing pharmacokinetic analysis including drug disposition, metabolism and clearance. The Bioanalytical Core will develop novel and innovative techniques for minimum sample preparation to allow rapid isolation and quantification of polar drug metabolites and glucuronide metabolites. If funded, it will develop a research program concerning micro sample preparation techniques such as ambient surface sampling by liquid microjunction surface sampling probe (LMJ-SSP), for MS detection and quantification of drugs or other small molecules in animal tissues and slices. This will allow the detection of drugs/metabolites in specific anatomical areas identified by imaging techniques. We further propose to enhance MSL capabilities to detect analytes at very low concentrations in biological specimens by the addition of micro sampling techniques combined with highly selective and sensitive MS instrumentation such as time of flight (TOF) detectors. Such MS systems decrease the lower limits of detection and improve the quantification of drugs of abuse and their metabolites at very low concentrations in biological specimens. The ability to detect very low drug concentrations will extend the time period for collection specimens for disposition/pharmacokinetic evaluations. The Bioanalytical Core will also collaborate